The role of remote ischemic preconditioning in the treatment of atherosclerotic diseases

Abstract

BackgroundRemote ischemic preconditioning (RIPC) is the application of a transient and brief ischemic stimulus to a distant site from the organ or tissue that is afterward exposed to injury ischemia, and has been found to reduce ischemia–reperfusion injury (IRI) in various animal models. RIPC appears to offer two distinct phases of endothelial IRI protection, which are presumably mediated through neuronal and humoral pathways.MethodsWe conducted a comprehensive literature review on the available published data about the potential effect of RIPC in patients undergoing IRI in one or more vital organs.ResultsOur search highlighted 24 randomized clinical trials about the effect of RIPC on variable clinical settings (abdominal aortic aneurysm repair, open heart surgery, percutaneous coronary intervention, living donor renal transplantation, coronary angiography, elective decompression surgery, carotid endarterectomy, recent stroke, or transient ischemic attack combined with intracranial carotid artery stenosis). Most of the trials focused on postoperative cardiac or renal function after RIPC with conflicting results. Preconditioning protocols, age limits, comorbidities, and concomitant drug use varied significantly across trials, and therefore no firm conclusions can be drawn using the available data. However, no severe local adverse events were observed in any patient undergoing limb or arm preconditioning.ConclusionsRIPC is a safe and well-tolerated procedure that may constitute a potentially promising innovative treatment in atherosclerotic diseases. Large, multicenter, randomized clinical trials are required to determine an optimal protocol for the RIPC procedure, and to evaluate further the potential benefits of RIPC in human ischemic injury.

Remote ischemic preconditioning versus intermittent hypoxia training: a comparative analysis for cardioprotection

“…NO, a known major adenosine-induced vasodilator, has also been associated with the protective effects of preconditioning [12,41]. Apart from locally induced vasodilation, NO may trigger other signal pathways and induce hepatic heme oxygenase-1 (HO-1), a stress inducible protein with anti-inflammatory effects.…”

“…RIPC appears to offer two distinct phases of endothelial IRI protection, both of which are mediated from the autonomic nervous system [12]. The early, short phase is activated immediately after preconditioning and vanishes within 4 h, whereas the second, prolonged phase presents 24 h after the preconditioning stimulus and lasts for at least 48 h [49,50].…”

“…Vasdekis [12] reviewed a total of 24 randomized clinical trials evaluating the safety and efficacy of RIPC in different atherosclerotic diseases including abdominal aortic aneurysm, open heart surgery, percutaneous coronary intervention, and intracranial or extracranial atherosclerosis. The findings indicate that an optimal protocol for the induction of RIPC has not been established.…”

“…The technique is physiologically sound but remains lacking in clear clinical benefit. Vasdekis et al [12] also conclude that most of the trials focused on postoperative cardiac or renal function after RIPC with conflicting results. However, no severe local adverse events were observed in any patient undergoing limb or arm preconditioning.…”

“…Among these attempts, remote ischemic preconditioning (RIPC) is known as a more convenient model for clinical usage. RIPC is the application of a transient and brief ischemic stimulus to a distant site from the organ or tissue that is afterward exposed to injury ischemia, and has been found to reduce ischemia-reperfusion injury in various animal models [12]. The standard protocols normally used to deliver RIPC involve a number of short cycles (about 5 min) of inflation of a blood pressure (BP) cuff on the arm and/or leg to an inflation pressure of 200 mmHg followed by cuff deflation for a short period of time [13].…”